Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Bioorg Med Chem Lett. 2010 Apr 1;20(7):2174-7. doi: 10.1016/j.bmcl.2010.02.041. Epub 2010 Feb 13.
This Letter describes the synthesis and SAR, developed through an iterative analog library approach, of a novel series of selective M(1) mAChR antagonists, based on an N-(4-(4-alkylpiperazin-1-yl)phenyl)benzamide scaffold for the potential treatment of Parkinson's disease, dystonia and other movement disorders. Compounds in this series possess M(1) antagonist IC(50)s in the 350 nM to >10 microM range with varying degrees of functional selectivity versus M(2)-M(5).
这封信描述了一种新型的选择性 M(1) mAChR 拮抗剂的合成和 SAR 研究，该拮抗剂是基于 N-(4-(4-烷基哌嗪-1-基)苯基)苯甲酰胺支架，为治疗帕金森病、肌张力障碍和其他运动障碍而开发的。该系列化合物具有 350 nM 至 >10 microM 的 M(1)拮抗剂 IC(50)，对 M(2)-M(5)具有不同程度的功能选择性。
